PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) was isolated as a tumor suppressor gene in 1997, and since then the physiological functions thereof have been analyzed from various viewpoints. It is reported in 1998 that the PTEN gene product exhibits a new phosphatase activity, i.e. it is able to dephosphorylate a phosphatidylinositol 3,4,5-trisphosphate (PIP3) substrate, which is a lipid second messenger, at D3 position thereof (cf. Beitner-Johnson D, Millhorn DE., J. Biol. Chem., 273: pp. 13375-13378, 1998).
In view of the functions of PTEN, it is expected that when inhibition of PTEN will be effective for promotion of the survival of normal cells, brain cells, heart cells, and skin, and further effective for inhibiting of Gram negative sepsis and cell migration and cell invasion.
Besides, it is known that the opening of potassium channel induces flowing the intracellular potassium ion out of cells which results in negative intracellular potential and that the potassium channel is voltage-dependent and is controlled intracellular calcium concentration and intracellular ATP. Maxi-K channel is a class of large conductance calcium sensitive potassium channels, and the activity of Maxi-K channels is controlled by intracellular calcium concentration and membrane potential, etc. The Maxi-K channels are widely distributed within the living body such as neurons, heart cells, smooth muscle cells, and the opening of the Maxi-K channels induces hyperpolarization of cells. It is also known that the opening of the Maxi-K channels is useful for the treatment of neuronal disorders, for example, as a medicament such as (1) an anticonvulsant, (2) a medicine for neuroprotection, for treatment of regional cerebral edema and neurologic motor impairment, cognitive disorders, traumatic brain injury, Parkinson's disease, epilepsy, migraine, and Alzheimer's disease, (3) a medicine for control of a pain, (4) a medicine for treating urge urinary incontinence, intestinal hypermotility, uterine contractility, anxiety, and depression.